Abstract: The present disclosure provides methods and compositions of altering a target nucleic acid sequence in a cell. The methods comprise introducing into the cell a guide RNA comprising a portion that is complementary to all or a portion of the target nucleic acid sequence, introducing into the cell a Cas9 transposase fusion protein, and introducing into the cell a donor nucleic acid sequence, wherein the guide RNA and the Cas9 transposase fusion protein co-localize at the target nucleic acid sequence, wherein the Cas9 transposase fusion protein cleaves the target nucleic acid sequence and the donor nucleic acid sequence is inserted into the target nucleic acid sequence in a site specific manner.

Abstract: The disclosure provides a method of modifying a PERV-A receptor gene in a cell. The method includes introducing into the cell a nucleic acid sequence encoding a Cas9 protein and a nucleic acid sequence encoding a guide RNA, introducing into the cell a donor nucleic acid sequence, wherein the Cas9 protein and the guide RNA are expressed and co-localize at a genomic site near or in the PERV-A receptor gene and the donor nucleic acid sequence replaces the PERV-A receptor gene by homology directed repair (HDR).